Field of the Invention
The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to several novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.
Description of Related Art
Acute myeloid leukemia (AML), also known as acute myelogenous leukemia or acute nonlymphocytic leukemia (ANLL), is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease, accounting for approximately 1.2% of cancer deaths in the United States, its incidence is expected to increase as the population ages.
The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection. Several risk factors and chromosomal abnormalities have been identified, but the specific cause is not clear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.
AML has several subtypes; treatment and prognosis varies among subtypes. Five-year survival varies from 15-70%, and relapse rate varies from 33-78%, depending on the subtype. AML is treated initially with chemotherapy aimed at inducing a remission; patients may go on to receive additional chemotherapy or a hematopoietic stem cell transplant.
US 2005/0261190 A1 discloses polypeptide fragments of Fas associated Factor 1, which bind to Hsc70/Hsp70, ubiquinated protein or valosin containing protein. Some of the fragments include SEQ ID NO: 5 as disclosed herein.
Similarly, KR100692416 discloses a fragment of FAF-1 (Fas-associated Factor 1) as having inhibitory effects on angiogenesis and cell proliferation. Therefore, it is proposed as an anticancer agent, e.g. a tumor metastasis inhibitory agent. The fraction having inhibitory effect on tumor metastasis is composed of 290-345 amino acids of FAF1.
Hassan et al. (The human leukocyte antigen-presented ligandome of B lymphocytes. Mol Cell Proteomics. 2013 Jul.; 12(7):1829-43) disclose the identification and relative quantification of 14,500 peptide ligands constituting the HLA ligandome of B cells as a starting point for solving a wealth of specific immunological questions.
Kowalewski et al. (Mapping The HLA Ligandome Of Chronic Lymphocytic Leukemia—Towards Peptide Based Immunotherapy Blood 2013; 122(21):4123) describe a method to analyse the HLA class I peptidomes of 25 CLL patients and 35 healthy controls.
Despite the above, there remains a need for new efficacious and safe treatment option for cancers such as blood cancer, in particular acute myeloid leukemia (AML) and other cancers of the blood of different phenotypes which improve the well-being of the patients by not using excessive chemotherapeutic agents or other agents that may lead to severe side effects.
The present invention employs peptides that stimulate the immune system of the patient and act as anti-tumor-agents in a non-invasive fashion.